ArticleTranslational neurodegeneration2018
GM604 regulates developmental neurogenesis pathways and the expression of genes associated with amyotrophic lateral sclerosis.
Article in Translational neurodegeneration, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- An Exploratory Study of High-Concentration Trace Amine Effects and Adrenoceptor Expression Patterns in SH-SY5Y Cells and Neuroblastoma.International journal of molecular sciences · 2026Article
- Extracellular Matrix Remodeling in Motor Neuron Diseases.International journal of molecular sciences · 2025Review
- Gene therapy breakthroughs in ALS: a beacon of hope for 20% of ALS patients.Translational neurodegeneration · 2025Review
- C21ORF2 mutations point towards primary cilia dysfunction in amyotrophic lateral sclerosis.Brain : a journal of neurology · 2025Article
- Depleting Cellular Retinoic Acid Binding Protein 1 Impairs UPRJournal of cellular signaling · 2023Article
- Multitarget Hybrid Fasudil Derivatives as a New Approach to the Potential Treatment of Amyotrophic Lateral Sclerosis.Journal of medicinal chemistry · 2022Article
- Therapeutic Peptides Targeting PPI in Clinical Development: Overview, Mechanism of Action and Perspectives.Frontiers in molecular biosciences · 2021Review
- Emerging neuroprotective strategies for the treatment of ischemic stroke: An overview of clinical and preclinical studies.Experimental neurology · 2021Review
- Post-Developmental Roles of Notch Signaling in the Nervous System.Biomolecules · 2020Review
- Sonic Hedgehog-Gli1 Signaling and Cellular Retinoic Acid Binding Protein 1 Gene Regulation in Motor Neuron Differentiation and Diseases.International journal of molecular sciences · 2020Article
- Correction: GM604 regulates developmental neurogenesis pathways and the expression of genes associated with amyotrophic lateral sclerosis.Translational neurodegeneration · 2020Article
- GM6 Attenuates Alzheimer's Disease Pathology in APP Mice.Molecular neurobiology · 2019Article
- ALS blood expression profiling identifies new biomarkers, patient subgroups, and evidence for neutrophilia and hypoxia.Journal of translational medicine · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAmyotrophic lateral sclerosis (ALS) is currently an incurable disease without highly effective pharmacological treatments. The peptide drug GM604 (GM6 or Alirinetide) was developed as a candidate ALS therapy, which has demonstrated safety and good drug-like properties with a favorable pharmacokinetic profile. GM6 is hypothesized to bolster neuron survival through the multi-target regulation of developmental pathways, but mechanisms of action are not fully understood.
methodsThis study used RNA-seq to evaluate transcriptome responses in SH-SY5Y neuroblastoma cells following GM6 treatment (6, 24 and 48 h).
resultsWe identified 2867 protein-coding genes with expression significantly altered by GM6 (FDR < 0.10). Early (6 h) responses included up-regulation of Notch and hedgehog signaling components, with increased expression of developmental genes mediating neurogenesis and axon growth. Prolonged GM6 treatment (24 and 48 h) altered the expression of genes contributing to cell adhesion and the extracellular matrix. GM6 further down-regulated the expression of genes associated with mitochondria, inflammatory responses, mRNA processing and chromatin organization. GM6-increased genes were located near GC-rich motifs interacting with C2H2 zinc finger transcription factors, whereas GM6-decreased genes were located near AT-rich motifs associated with helix-turn-helix homeodomain factors. Such motifs interacted with a diverse network of transcription factors encoded by GM6-regulated genes (
conclusionsOur findings support the hypothesis that GM6 acts through developmental-stage pathways to influence neuron survival. Gene expression responses were consistent with neurotrophic effects, ECM modulation, and activation of the Notch and hedgehog neurodevelopmental pathways. This multifaceted mechanism of action is unique among existing ALS drug candidates and may be applicable to multiple neurodegenerative diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.